Acute renal failure is still a common and serious complications following shock, trauma and sepsis. The objectives of these studies are to: 1) Characterize the renal vascular response following ischemic-induced acute renal failure; 2) Elucidate the mechanism responsible for the sustained reduction in renal blood flow and glomerular filtration failure in acute renal failure; 3) Evaluate pharmacological and physiological means of reversing immediately, or minimizing, the renal dysfunction associated with acute renal insufficiency; and 4) Evaluate further the renal vascular response and altered renal function associated with sepsis. The effects of renin depletion and angiotensin blockade and the course of warm ischemic-induced acute renal failure in dogs will be studied. Renal blood flow measured by a flow transducer, and renal renin production measured by radioimmunoassay, will be obtained, following acute renal failure, and the effects of various pharmacological agents such as furosemide, mannitol and propranolol on flow and renin production will be evaluated. The effects of sepsis on the course of acute renal failure will be studied, including the renal hemodynamics effects of venous blood from a septic leg, and also the effects of endogenous leukocyte pyrogen. In vitro studies, using an isolated perfused hind limb preparation and a smooth muscle strip superfusion preparation, will be performed on venous blood from an ischemically injured kidney to determine if vasoactive substances are present. Hopefully, these studies will clarify the pathophysiological mechanisms involved in the etiology of acute renal failure, and provide the information necessary to develop methods of reversing the renal dysfunction immediately, thereby redically revolutionizing the treatment of this lethal complication.